The present invention relates to equipment for imaging and measuring information of a light scattering object, particularly, information inside a biological body using light.
A system which can measure blood circulation, blood circulation movement and oxygen metabolism inside a biological body with a low restraint to a test object (a person to be tested) and without causing harm to the biological body is required in a field, such as clinical medicine, and also brain science. When, for example, the head is an object to be measured, the measuring of a brain disease, such as the cerebral infarction, cerebral hemorrhage and insanity, as well as the measuring of a higher level brain function, such as thinking, language and exercise can be raised as specific needs. Also, such a measured object is not limited to the head, so that preventive diagnosis in connection with heart disease, such as myocardial infarction, as used for measuring the breast, to an internal organ disease, such as kidney disease and liver disease, as well for measuring the abdomen, and further measuring of oxygen metabolism in the muscle of the hand and foot can be raised as specific needs.
In the case where the head is a measured object, in the measurement of brain disease or a higher level brain function, it is necessary to clearly specify a zone of the diseased portion or a zone of the brain function. Therefore, the imaging measurement of the brain becomes important.
Of course, the importance of imaging measurement is not limited only to the brain, but the same can be said to apply to the measurements of the beast, the abdomen and so on.
As examples, it can be mentioned that the positron emission tomography (PET) and the functional magnetic resonance imager (fMRI) and the cerebral magnetic field measurement system (MEG) are widely used in the imaging measurement of the brain function. These systems have an advantage in that an active zone inside the brain can be measured as an image, but, on the other hand, they have a disadvantage in that the systems are large in size and the operation is very complex. For example, a large dedicated room is required to install the system, and, of course, it is difficult in practice to frequently move the system. Further, the restraint to the tested person is very high, because the tested person is forced to maintain a fixed posture for a long time inside the system during measurement; and, accordingly, he or she is forced to withstand a certain amount of mental and physical pain. Furthermore, the cost required for operating the system is large because a dedicated person to maintain and manage the system is required.
On the other hand, as a method of measuring blood circulation, blood circulation movement and oxygen metabolism inside a biological body with a low restraint on the tested person and without causing harm to the biological body (non-infestation), optical measurement is very effective. The first reason is that the blood circulation and the oxygen metabolism in a biological body correspond to a concentration and a change in the concentration of a specific pigment (hemoglobin, cytochrome, myoglobin etc.) in the biological body, and the concentration of the pigment can be measured from an amount of absorption of light having wavelengths within a range from visual to infrared light. The blood circulation and the oxygen metabolism are indicative of a normal or abnormal condition of the organ in the biological body and further indicate activity of the brain in regard to a higher level brain function. In addition, the second reason for the effectiveness of optical measurement is that the system can be made small in size and the measurement can be easily performed because of the technological development of laser diodes, light emitting diodes and photodiodes. Further, the fixing of the head during measurement becomes unnecessary by employing highly flexible optical fibers in the measurement, and, accordingly the restraint of the tested person can be largely reduced and the mental and physical pain endured by the tested person can be largely reduced. Furthermore, the third reason is that the optical measurement does not cause harm to the biological body when using light having an intensity within a safety standard range.
In addition to the advantages described above, the optical measurement has advantages of real time measurement, quantification of pigment concentration in a biological body and so on which the PET, the fMRI and the MEG do not have. In making use of these advantages of the optical measurement, systems which measure the inside of a biological body by illuminating light having wavelengths within a range from visual to infrared light onto the biological body and detecting reflected light from the biological body are disclosed, for example, in Japanese Patent Application Laid-Open No. 57-115232 and Japanese Patent Application Laid-Open No. 63-275323. Further, systems for imaging a biological body using optical measurement are disclosed in Japanese Patent Application Laid-Open No. 7-79935, Japanese Patent Application Laid-Open No. 9-19408 and Japanese Patent Application Laid-Open No. 9-149903. Furthermore, the effectiveness of the imaging measurement on a biological body using light is described, for example, in an article entitled xe2x80x9cSpatial and temporal analysis of human motor activity using noninvasive NIR topographyxe2x80x9d, by Atsushi Maki et al., Medical Physics, Vol. 22, pages 1997 to 2005 (1995).
In the non-invasive imaging measurement of a biological body using light, it is necessary to illuminate light beams onto a plurality of positions and to detect light beams from a plurality of positions. In that case, in order to further improve the optical measurement so that it is higher in accuracy and higher in sensitivity, additional circuits, such as a modulation adding, a modulation measuring, a temperature control, an optical intensity control, and temperature compensating circuits are necessary for the opt-semiconductor elements, such as a laser diode and a photodiode. Therefore, it is difficult to mount such an opt-semiconductor element directly on the test object. In order to make such measurement practically possible, light illumination and light detection using many optical fibers are required. However, Japanese Patent Application Laid-Open No. 7-79935 does not disclose in what arrangement each of the plurality of optical fibers used for the measurement is mounted on the test object in order to perform the desired image measurement.
On the other hand, in Japanese Patent Application Laid-Open No. 9-19408 and Japanese Patent Application Laid-Open No. 9-149903 and the cited article in Medical Physics, methods of efficiently arranging optical fibers on a test object are disclosed in detail. According to these methods, assuming that a square area having a side of 6 cm in the head is measured as a limited zone, four incident optical fibers for each of four incident positions and five detecting optical fibers for each of detection positions, that is, nine optical fibers in total, are necessary. Therefore, since the measurement position is a midpoint between the incident position and the detection position adjacent to each other, twelve measurement positions in total are set. In the field of the clinical medicine and the brain science, it is required to measure brain activity in a wide region. When a square area having a side of 12 cm is intended to be measured by applying the above-mentioned method of arranging the incident positions and the detection positions, twelve incident optical fibers and thirteen detecting optical fibers, that is, twenty-five optical fibers in total are necessary. When the measured area is further expanded, the number of optical fibers to be mounted is further increased and exceeds 100 depending on the circumstances. The prior art described above shows a part of the measurement principle in the non-invasive imaging measurement of a biological body using light, but does not disclose any display nor any function for the operator to efficiently mount the optical fibers.
When a large number of optical fibers are mounted onto a test object, the optical fibers can not be arranged on the test object in random. Firstly, at least, it is necessary that the incident optical fibers connected to light sources are mounted at the incident positions and the detecting optical fibers connected to photodetectors are mounted at the detection positions. Further, a correct image can not formed unless information on the light from which light source is incident to which position of the test object and on which detector detects light from which position of the test object is made clear for each of the incident and the detecting optical fibers. Therefore, the optical fibers to be mounted to all the incident positions and the detection positions need to be uniquely determined. When the number of optical fibers to be mounted is several tens to one hundred, it is difficult for the operator to speedily perform the work by correctly judging which optical fiber is to be mounted to which position of the test object. For example, if the operator works while finding the optical fiber for each of the positions to be connected one by one, it takes quite a long time to connect all the optical fibers. Accordingly, not only will the efficiency of measurement be decreased, but both the operator and the test object (the test person) will be physically and mentally exhausted. From the above, the first problem to be solved by the present invention is to provide an imaging measurement system which is non-invasive to a biological body using light which is capable of efficiently mounting many optical fibers.
The second problem to be solved by the present invention is to improve the reliability in the imaging measurement mounting many optical fibers. A system for efficiently displaying a state of a detection signal level which influences the reliability and for efficiently displaying the change in the state is provided. An example of the second problem will be described below.
The system described in Japanese Patent Application Laid-Open No. 9-149903 simultaneously performs a multichannel measurement of plural positions and plural wavelengths necessary for the imaging measurement of a concentration change in the pigment contained in a biological body, such as hemoglobin and the like. The simultaneous measurement is necessary for biological body measurement, particularly, for brain function measurement, in order to attain a high resolution over time. The outline of the system described in Japanese Patent Application Laid-Open No. 9-149903 is shown in FIG. 4. In this system, light is incident on a test object from a plurality of incident position s at the same time, and light is detected at a plurality of detection positions at the same time. Although the technique of measurement of plural wavelengths is omitted in FIG. 4, the measurement of plural wavelengths can be realized by applying the construction of this system in principle. In that case, the intensity of the light is modulated by a different frequency for each of the incident positions. For example, the modulation frequencies of the light incident on the incident positions 1, 2, 3 and 4 in FIG. 4 are f1, f2, f3 and f4. Therefore, each of these modulation frequencies is positional information corresponding to each of the incident positions. Although the light detected at the detection position 1 contains modulated light, the optical measured signal in regard to the positional information can be separately measured by measuring each of the modulation frequency signals selectively from the light output from the photodiode using a filter circuit, such as a lock-in amplifier or the like. For example, letting the detection signal levels be I1, I2, I3 and I4 for the modulations f1, f2, f3 and f4 detected by the photodiode corresponding to the detection position 1, respectively, each of the signals in the outputs of the lock-in amplifiers in synchronism with the individual frequencies is completely separated. As a result, efficient multichannel simultaneous measurement can be realized without interference between the signals, that is, without cross talk.
However, when an image is finally obtained from such measurement, a high accuracy of measurement is required for each of the signals. For example, if there is a signal having a very low measuring accuracy, that is, a very low S/N ratio, the reliability of a measurement position on the image corresponding to the signal is largely decreased. Thereby, the reliability of the image itself is also decreased. Therefore, a high accurate measurement having a good balance in S/N ratio over all the detection signals is required. However, the conventional system has the following problem in regard to the measuring accuracy.
In general, the state inside a biological body is optically heterogeneous. When the incident position or the detection position is placed in a portion having a large amount of hemoglobin of light absorbent material, such as a large blood vessel, attenuation of light becomes large and the corresponding detection signal level is largely reduced. The other causes which reduce the signal level in a specific measurement channel, as described above, are a case where the end surface of the optical fiber used for the measurement is optically stained; a case where the optical fiber is damaged, for example, the optical fiber is broken at a midpoint; and a case where there exists a problem in the state of mounting the optical fiber, for example, where hair comes between the optical fiber and the skin of the person to be tested.
Description will be made below on how the N/S ratio of the measurement is affected when a part of the detection signal level is largely decreased, and there is an unbalance in the detection signal levels as a whole.
In general, a shot-noise of a photodetector, such as a photodiode, is in proportion to the square root of the total amount of light arriving at the detector, that is, the total sum of the detected optical intensities. Here, it is assumed that of the detection signal levels I1, I2, I3 and I4 measured at the detection position 1 in FIG. 4, the detection signal levels I1, I2 and I3 are nearly equal (I1xcx9cL2xcx9cI3) and only the detection signal level L4 is smaller than the others by 1 order (I1 greater than  greater than I4). This situation is assumed for a case where there is a blood vessel at a position near the incident position 4 or a case where there is a problem in mounting the optical fiber at the incident position 4. In this case, the noise detected by the photodiode is mainly in proportion to the square root of the total sum of the detected intensities (I1+I2+I3+I4). Therefore, the originally low signal level of I4 is largely reduced in S/N ratio by being strongly affected by the strong signal levels of I1, I2 and I3. In order to describe this phenomenon further in more detail, a case is considered in which the signal level of I4 is not changed and the signal levels of I1, I2 and I3 are further increased. In this case, in regard to I4, the signal level, that is, S, is not changed, but the noise level N is increased. As a result, the S/N ratio of the signal in regard to I4 is further deteriorated. On the other hand, the S/N ratios in regard to the strong signal levels of I1, I2 and I3 are improved. Therefore, when a plurality of light signals are detected by a single photodetector, a large difference in the S/N ratio is caused among the measured signals.
In addition to this, the following problem occurs in the measurement performed by this method. In a case where many strong detected light signals, for example, such as the signals I1, I2 and I3 described above, are contained in a detection signal, because of the limitation of the dynamic range of the detector, such as a photodetector and a lock-in amplifier, there are some cases where the total sum of the detected light signals exceeds the dynamic range. The dynamic range is specified by a range in which the linear response property of the measurement equipment is guaranteed. However, even if the signal level exceeds the dynamic range, a finite value is sometimes output from the detector. However, the value in that case is very low in the reliability of the measurement.
As described above, when a large difference occurs between the detection signal levels, the S/N ratio of each of the signals becomes large. When an image is formed using these signals, the reliability of the image is decreased. In the case where there is a strong detected light signal among these signals, the detected light signal exceeds the dynamic range of the detector, thereby to deteriorate the reliability of the measurement itself.
The second problem to be solved by the present invention is to provide a highly reliable measurement system to effect multichannel simultaneous measurement of plural positions and plural wavelengths, which realizes a high time-resolution in the non-infestation imaging of a biological body using light. In the case where there is a cause for unbalance of the measured signals resulting in a decrease of the reliability, such as a stain or a damage in the optical fiber or a problem in the mounting state of the optical fiber, it is generally very difficult to find the corresponding fiber and the corresponding position among the large number of several tens to about 100 mounted optical fibers. Therefore, the second object of the present invention is to provide a system which makes it easy for the operator to solve the problem of mounting the optical fibers by easily, clearly and effectively displaying the corresponding optical fiber, when there is the problem in an optical fiber or in the mounting state of an optical fiber.
The third problem to be solved by the present invention is to always maintain the high reliability of the measurement even during the measurement.
There are some cases where the detection signal level is largely changed during measurement, for example, of a person""s head, due to a large physiological change, such as a change in a blood flow rate or due to occurrence of sudden displacement of a probe mounting the optical fiber. When the detection signal level exceeds the appropriate dynamic range of the measurement equipment as a result, the effectiveness of the measurement may be lost. Further, since there are some cases where it is difficult to repetitively perform a measurement depending on the physiological state of a test body, it is necessary to perform and complete the measurement with a high reliability once the measurement is started. The third problem to be solved by the present invention is to provide a system capable of solving the above-mentioned need.
In order to solve the first problem described above, in regard to incident positions of light on a test object and detection positions of light from the test object and measurement positions determined by spatial arrangement between the incident positions and the detection positions, a relative positional relationship among the positions and a state of detection signals or a change in the state are displayed on a display unit. On the display unit, the incident positions, the detection positions and the measurement positions are individually displayed by graphic elements, and these graphic elements are arranged in a specified frame-shaped picture. In this regard, the state of the detection signals or a change of the state or a fluctuation per unit time of the state is displayed so as to be identified by a changing color or pattern of the graphic elements on the display unit. This identification display method is specific to the non-invasive imaging measurement of a biological body using light. Further, the optical measurement system comprises an optical illuminating means to illuminate the test object, an optical detection means for detecting light returned from the test object, and display elements in probes to mount these means on the test object, and the display elements are operated in an interlocking manner with the display of the graphic elements on the display unit. Further, in order to make it possible for an operator to easily understand the spatial arrangement of the incident positions and the detection positions and the measurement positions, graphic elements expressing the incident positions and the detecting positions and the measurement positions are displayed by superposing the graphic elements on an image representing a shape of the test object or information on an inside portion of the test object.
Further, in order to solve the second problem, prior to performing the regular measurement involving multichannel simultaneous measurement at a plurality of positions and with a plurality of wavelengths, as a preparation for the measurement, light is sequentially incident on the test object for each of the incident positions and for each of the wavelengths, and signal levels of the detection light are measured for each of the incident positions and for each of the wavelengths. Further, the amplification factor of each of the amplifiers and each of the optical intensity levels are independently changed for each of the incident positions and for each of the wavelengths so that each difference between the detection signal levels measured for each of the incident positions and for each of the wavelengths may fall within an appropriate range. The amplification of each of the signal levels or each of the optical intensity levels is changed so that the total sum of the detection signal levels relating to each of the measurement instruments may fall within an appropriate range.
When light is illuminated as the preparation measurement for each of the incident positions or for each of the wavelengths, each incident optical intensity is continuously increased from the zero level up to a set intensity level, and the detection signal level relative to the change in the optical intensity is continuously detected. At that time, when the response of the detection signal level to the incident light intensity level becomes non-linear, the incident light intensity level is decreased to a set level. In the course of the preparation measurement, when the detection signal level is out of the appropriate range, the corresponding incident position and the corresponding detection position and the corresponding measurement position are shown by a change in color or pattern of the graphic elements on the display unit. In addition, the corresponding incident position and the corresponding detection position are also displayed in the display elements of the optical illuminating means and the optical detection means and the probe.
Further, in order to solve the third problem, when the detection signal level is out of the appropriate range in the regular measurement performing process for measurement of a pigment, such as hemoglobin, in a biological body, the corresponding incident position and the corresponding detection position and the corresponding measurement position are displayed by a change in color or pattern of the graphic elements on the display unit. Further, the corresponding incident position and the corresponding detection position are also displayed in the display elements of the optical illuminating means and the optical detection means and the probe. When the detection signal level is further out of the appropriate range, the amplification factor of the amplifier relating to the detection signal or the optical intensity level of the corresponding incident light is automatically changed at a set rate.
In the solutions of the problems described above, programs for executing the display and the measurement described above are recorded in a computer-readable recording medium.